Month: November 2014

If you ate a big Thanksgiving dinner yesterday, you probably felt drowsy and sluggish afterward, a phenomenon often referred to as a “food coma”. The belief that it’s caused by the tryptophan in turkey is a long busted myth, and in fact it can happen after any carb-heavy meal. The reasons for this post-food slump are relatively well understood from experiments in humans and other mammals. For one, big meals trigger a “rest and digest” response when the food reaches the stomach and small intestine (via activation of the parasympathetic nervous system). This diverts energy to digestion, making you feel sluggish and sleepy. But wait, there’s more! Eating a meal full of carbs and other sugars also stimulates the release of insulin, which triggers a process to take up nutrients from the bloodstream. But a side effect of this process is an increase in the amount of serotonin and melatonin in the brain, two chemicals that are associated with drowsiness (and often happiness).

So having a full stomach makes you sleepy, but did you know that the relationship between sleep and food goes deeper than that? For example, studies in animals from fruit flies all the way to humans have shown that having an empty stomach can keep you awake. Even worse, chronic sleep deprivation stimulates appetite and can lead to weight gain. Studies in humans have uncovered strong correlations between sleep disorders like insomnia and obesity-related disorders such as diabetes and cardiovascular disease. One of the reasons for this is that sleep loss wreaks havoc on the levels of certain hormones, such as the “hunger hormone” ghrelin.

Thus, even though sleeping and eating are mutually exclusive behaviors (you can’t sleep while you’re eating), they’re also obviously connected. Both are essential for survival, so the brain may often be promoting at least one of them. But how does the brain decide which behavior is more important at any given time? When you’re hungry, it seems more important to stay awake and find food to prevent starvation, but sleep deprivation also has health consequences, so the brain needs to ensure you get enough sleep.

So how are sleep and hunger connected in the brain? Are they independent, so that hunger suppresses sleep, and sleepiness stimulates hunger? Or maybe they arise from the same mechanism, which signals in turn for either sleep or eating depending on your body’s needs. Answering this question will improve our understanding of sleep- and obesity-related disorders and how they’re linked, a necessary step before treatments can be developed.

Fruit flies make a great animal model for answering detailed questions like these, which take place on a molecular and cellular scale. Although much research has yet to be done, there have already been some informative findings. For starters, scientists have found that insulin-producing cells in the fly brain regulate both feeding and sleep, providing a cellular link between these two behaviors (remember that insulin’s activities are partially responsible for the food coma after Thanksgiving dinner). Their findings suggest that these cells integrate information from other brain regions about sleep need and hunger, and may even potentially act as a “behavioral switch” to signal which behavior is more important at any given time.

Other fruit fly researchers have found a link between eating and sleeping in a single molecule called “NPY-like short neuropeptide F” (sNPF). sNPF had already been shown to regulate food intake, but recently it was found that sNPF also promotes sleep. sNPF is similar to a mammalian chemical called “neuropeptide Y” (NPY), which also plays a little-understood role in sleep and eating in mammals. NPY has recently been studied as a possible drug target for obesity treatment in humans even though its role in other behaviors is unclear, so a better understanding of this chemical is essential to account for possible side effects such as sleep disruption.

Research in a variety of animal models (and humans) has shown us that sleep and hunger are related. Overall, the combined results of fruit fly research suggests that sleep and feeding behaviors may arise from shared mechanisms in the brain. Future studies will pin down the exact mechanisms and apply those findings to more complex mammalian systems. Hopefully, this research will lead to the development of drugs that can help with sleep- and obesity-related disorders. In the meantime, I think I’ll try drinking coffee with Thanksgiving dinner.

Every year, over 30,000 neuroscientists gather at the Society for Neuroscience annual meeting to present their latest research and catch up with long-lost colleagues. This year’s meeting took place November 15-19th at the Walter E. Washington Convention Center in Washington DC. The meeting is often dominated by researchers working with mammalian models (we Drosophila researchers often attend conferences specific to our model instead), but invertebrate scientists still make a good showing every year. And this year’s meeting was a great one for fruit flies!

This year, two of the Special Lectures were dedicated to fruit fly research. First, Dr. Amita Seghal presented her lab’s latest sleep research showing that young flies need more sleep for normal brain development (I reviewed their latest paper). This finding highlights how important it can be for children of all species (including humans) to get enough sleep. Later in the week, Dr. Vivian Budnik presented her lab’s discoveries on the mechanisms neurons use to form stable connections (called synapses) and talked about how problems in these processes in humans can lead to disease.

Fruit fly researchers also presented over 100 posters and gave several short talks on a range of topics, from basic molecular and cellular research to complex behavioral studies, such as how sleep and memory can arise from a network of cells. Although it can sometimes be hard to imagine how fruit fly research could be relevant to humans, research in this animal model often has important implications for human diseases. In particular, fly researchers presented in several sessions related to Alzheimer’s disease this year, and they also showed up in sessions for other human diseases such as schizophrenia, Parkinson’s disease, and autism. In fact, a fly poster about a possible new treatment for a genetic form of autism was highlighted in a SFARI post by blogger Virginia Hughes (also an official blogger for SFN 2014).

Did you see (or present) any fascinating or surprising fruit fly research at SFN this year? Leave a comment below!

As human life expectancy continues to increase at a steady rate in most countries worldwide, the prevalence of aging-related diseases is also increasing. One such example is Alzheimer’s disease (AD), the most common cause of dementia in the aging population. There is currently no cure for AD, and the only treatments that exist temporarily cover up the symptoms without actually slowing the disease itself.

Alzheimer’s disease can be identified by the abnormal accumulation of a protein called amyloid beta (Aβ) in the brain. Aβ is a byproduct of an important cellular process, and is usually cleared away by the cell’s garbage recycling processes. It’s normal for some leftovers to be missed, however, and over time Aβ builds up as we age. But in large enough concentrations—such as in older patients with AD—accumulation leads to the formation of aggregated deposits of Aβ. These deposits damage neurons and cause neurodegeneration (progressive neuron death).

The left side shows healthy neurons. The right side shows damaged neurons and Aβ deposits as seen in Alzheimer’s disease patients. Image modified from alz.org

Eventually, this widespread brain tissue damage leads to imbalances in the levels of neurotransmitters, which are chemicals that neurons use to communicate. This imbalance is thought to cause the symptoms of AD, including problems with memory, thinking, or changes in behavior. Current treatments simply alter the amount of these neurotransmitters without doing anything to slow or prevent Aβ aggregation and neuron death. Therefore, research aimed at developing a drug that can interfere with Aβ accumulation is important for treating this disease.

Recent findings in lithium research holds hope for such a treatment. Although lithium is most widely used as a treatment for bipolar disorder, some preliminary research suggests that it might also be able to slow or prevent the symptoms of Alzheimer’s disease in humans if prescribed early enough. However, the results have been mixed and even sometimes contradictory. This is largely due to the fact that lithium’s actions in the brain are not understood, so figuring out how lithium might be helping AD patients is essential before it could be considered as a treatment. A recent paper published in Frontiers of Aging Neuroscience by the Partridge lab has begun to do just that by studying how lithium can reduce Aβ accumulation in a fruit fly model of Alzheimer’s disease.

The authors created a model for AD by introducing a mutated form of human Aβ protein known to cause AD in some families (called Arctic Aβ42) into adult fruit flies. Flies with the Arctic Aβ42 mutation displayed progressive neuron dysfunction and shortened lifespan, which mimicked the symptoms of AD in human patients. They had previously shown that lithium treatment was able to reduce the amount of Aβ (and thus also its toxic effects on neurons) in these flies. But how did it work? In this study, they treated these mutant flies with lithium again to answer this question.

What they found was surprising. Lithium didn’t just reduce the amount of Aβ protein in the brain, it reduced the amount of all proteins. It worked by suppressing the activity of the “translation machinery”, which refers to the system that actually assembles and produces proteins from the instructions in the genetic code. So lithium actually reduced the production of all proteins through a mechanism that wasn’t specific to Aβ.

What does this mean for the possibility of using lithium to treat Alzheimer’s disease? The fact that lithium’s effects are more general is actually pretty good news not just for AD, but for all research into the aging process. It is currently thought that normal aging is caused by the accumulation of damaged or mutated proteins that haven’t been cleaned up, and research aimed at increasing lifespan has focused on either improving the cell’s recycling processes or reducing protein production. In fact, lithium treatment has been shown to increase life expectancy in animal models, including fruit flies (and possibly even in humans!).

So if lithium can increase lifespan in animals without Alzheimer’s disease, can it reverse the lifespan reduction in the AD model flies? Yes! The authors found that lithium treatment also improved the life expectancy of their mutant flies compared to ones that did not get a lithium treatment. This result provides further hope that lithium could one day be used to actually slow the progression of AD and give patients more years of quality life.

The findings in this paper are not just promising for Alzheimer’s disease, but also for other aging-related diseases caused by abnormal accumulation of protein in the brain, such as Parkinson’s disease and Huntington’s disease. Lithium also has the advantage of already being an approved drug for treating patients with bipolar disease, so some information on side-effects and dosages already exists. Of course, this doesn’t mean doctors should begin prescribing lithium for AD patients right away; the dosage requirements will likely be different and older adults may experience other side-effects. But research in this field has definitely leapt forward, and we may see a cure for aging-related diseases in our (extended?) lifetime.

Have you ever wondered how our body recognizes when it’s being invaded by harmful bacteria? Nearly all forms of life—from single-celled organisms all the way to humans—have an “innate” immune system, which has evolved to recognize cellular components shared by broad groups of pathogens. One such example is peptidoglycan, a molecule found on the cell walls of virtually all bacteria. Peptidoglycan forms a sort of “load-bearing mesh” required for the bacteria to maintain their shape and is therefore an essential part of their structure. As a result, our immune systems have evolved to recognize peptidoglycan as a danger signal and will trigger an immune response when it is detected.

But just as our innate immune system has evolved to recognize invaders bearing peptidoglycan, bacteria have also evolved to escape detection. In a recent paper published in eLife by the Filipe lab, researchers used fruit flies to study how some bacteria can remain undetected by its host. Understanding how bacteria avoid detection will help us develop new ways to defeat them by preventing them from evading our immune system. This could reduce the need for antibiotics, which is particularly important now that antibiotic-resistant bacteria are becoming painfully common (in 2014, the World Health Organization declared antibiotic resistance a major threat to public health).

The difference between Gram-negative and Gram-positive bacteria. Image source

So how do bacteria with peptidoglycan conceal themselves from our immune system? Previous work has categorized bacteria into two groups based on the way they cover up their peptidoglycan mesh: Gram-negative bacteria, which have a full membrane surrounding the peptidoglycan molecules, and Gram-positive bacteria, which have the mesh directly outside the cell wall. Instead of a full membrane, Gram-positive bacteria have layers of molecules that stick out of the cell wall and block access to the peptidoglycan. Because of this, it has long been thought that the immune system can only detect peptidoglycan when fragments have been snipped off of the bacterial walls (when bacteria need to grow and divide, they must break down their mesh and then rebuild it).

But now, researchers have uncovered a new twist to this story. Recent findings have suggested that under certain conditions, the immune system can actually recognize peptidoglycan while it’s still a part of the bacterial cell wall. So the authors of this paper asked: Have bacteria evolved other methods to prevent this from happening?

To answer this question, they infected fruit flies with Staphylococcus aureus (S. aureus), a Gram-positive strain of bacteria related to MRSA. They observed how well the fruit fly hosts were able to defend against the invaders, and then mutated parts of the bacteria to determine how each manipulation affected the hosts’ ability to survive. The authors learned that S. aureus releases a molecule called Atl, which they found was responsible for trimming off pieces of peptidoglycan that stick up above the bacteria’s protective layer. When the bacteria couldn’t release Atl, the flies were much more likely to survive the infection because their immune system could more easily recognize the intruders and fight them off.

How can this help us humans? The mammalian innate immune system is similar to that of flies, and also recognizes peptidoglycan as a trigger for activating an immune response. Thus, if bacteria that infect humans use the same evasive maneuvers, it could be possible to develop a drug that targets and disables Atl and other peptidoglycan-snipping molecules. This would allow our immune systems to better recognize and fight back against bacterial infections and reduce the need for antibiotics.

The authors have already done some of the work toward this goal. To find out if strains of bacteria known to endanger humans use the same avoidance mechanism, they also infected flies with MRSA, a dangerous antibiotic-resistant strain of bacteria often found in hospitals, and Streptococcus pneumoniae, which is a frequent cause of pneumonia in developed countries and a major cause of infant mortality in developing countries. That found that both of these bacteria use Atl to shave their surface and avoid recognition by the immune system. Future research may therefore lead to treatments that prevent these bacteria from going into hiding, allowing our immune system to hunt them down and do its job with ease.